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Functional Challenges for Technology Fraser Armstrong1, Kylie A J Biol Inorg Chem (2007) 12 (Suppl 1):S53–S98 DOI 10.1007/s00775-007-0256-4 2. METALLOPROTEINS DNA; the properties of two of these enzymes (hABH1 and hABH5) are described. KEYNOTE LECTURES KL10 KL08 Towards the Mechanism of N2 Reduction by Nitrogenase Electrocatalytic hydrogen cycling by hydrogenases in the Brian M. Hoffman, Northwestern University, Evanston, IL, USA. Contact e-mail: [email protected] presence of O2: functional challenges for technology Fraser Armstrong1, Kylie A. Vincent1, James A. Cracknell1, 1 1 2 A major obstacle to understanding the reduction of N2 to NH3 by Annemarie Wait , Gabrielle Goldet , Baebel Friedrich , Oliver nitrogenase has been the impossibility of synchronizing electron Lenz2, Marcus Ludwig3, 1University of Oxford, Department of 2 delivery to the MoFe protein so that intermediates along the N2 Chemistry, Oxford, United Kingdom; Institut für reduction pathway can be accumulated for characterization. Biologie/Mikrobiologie, Humboldt-Universität zu Berlin, Germany; 3 Recently, however, in a collaboration with the groups of Dennis Institut für Biologie/Mikrobiologie,, Humboldt-Universität zu Dean and Lance Seefeldt, a number of intermediates have been Berlin, Germany. trapped by freeze-quenching, and ENDOR spectroscopy has proven Contact e-mail: [email protected] to be the method of choice for characterizing substrate-derived species bound to FeMo-co of trapped enzymatic intermediates. This Hydrogenases are usually inactivated under oxidizing conditions presentation will describe current understanding of the structure of [1]. Yet many aerobic microbes obtain energy using [NiFe]- trapped intermediates and of the mechanistic sequence of hydrogen hydrogenases that can oxidize traces of H in air [2,3]. Enzymes 2 addition to N2. from Ralstonia have such high selectivity for H against O that 2 2 Even when an intermediate is trapped, the process of electron they can be used as electrocatalysts in the simplest of fuel cells- delivery requires that this occur without synchronous electron lacking a membrane or even just an anode and cathode separated by delivery, and as a result the number of electrons (and protons), n, an electrolyte film [4,5]. Using a ‘blue’ Cu oxidase, laccase as that has been accumulated during its formation is unknown. cathode catalyst, sufficient power is produced from 3% H in air to 2 Consequently, the intermediate is untethered from Lowe-Thornely power a wristwatch - not a high demand, but a visible and (LT) kinetic schemes for reduction, which are indexed by n. We demanding test of a hydrogenase’s ability to function in air. This have shown that a trapped intermediate itself provides a lecture addresses how these hydrogenases function in low levels of 'synchronously prepared' initial state whose relaxation to the resting H . 2 state under conditions that prevent electron delivery to MoFe 1. K. A. Vincent, A. Parkin, O. Lenz, S. P. J. Albracht, J. C. protein can be analyzed to disclose n and the nature of its relaxation Fontecilla-Camps, R. Cammack, B. Friedrich and F. A. Armstrong, reactions. We will describe the relaxation protocol and outline J. Am. Chem. Soc. (2005) 127, 18179. current understanding of the connections of trapped nitrogenous 2. T. Burgdorf, O. Lenz, T. Buhrke, E. van der Linden, A.K. Jones, intermediates to the LT kinetic scheme for N2 reduction, as well as S.P.J. Albracht and B. Friedrich, J. Mol. Microbiol. Biotech. (2005) the mechanisms by which intermediates relax. 10, 181. 3. K. Knuttel, K. Schneider, A. Erkens, W. Plass, A. Muller, E. Bill and A.X. Trautwein, Bull. Polish Acad. Sci.-Chem. (1994) 42, 495. KL11 4. K. A. Vincent, J. A. Cracknell, O. Lenz, B. Friedrich and F. A. Armstrong, Proc. Natl Acad. Sci. USA, (2005) 102, 16951-16954. Copper Prion Interactions. Specificity from mammalians 5. K. A. Vincent, J. A. Cracknell, J. Clark, O. Lenz, M. Ludwig, B. to Fishes 1 1 1 Friedrich and F. A. Armstrong, Chem. Commun. (2006) 5033-5034. Henryk Kozáowski , Anna Janicka , Paweá StaĔczak , Daniela Valensin2, Gianni Valensin2, 1Faculty of Chemistry, University of Wroclaw, Wrocáaw, Poland; 2Department of Chemistry, University KL09 of Siena, Siena, Italy. Fe(II)/2-oxoglutarate-dependent hydroxylases Contact e-mail: [email protected] Robert P. Hausinger1, Piotr K. Grzyska1, Meng Li2, Jana M. Prion diseases are fatal neurodegenerative disorders including Simmons3, Tina A. Müller1, 1Michigan State University, spongiform encephalopathies in cattle and sheeps and Creutzfeld- Microbiology and Molecular Genetics, East Lansing, MI, USA; Jacob syndrome in humans. Although biological functioning of 2Michigan State University, Chemistry, East Lansing, MI, USA; prion protein (PrP) is still unknown it seems to be generally 3Michigan State University, Biochemistry and Molecular Biology, accepted that it may play a critical role in copper homeostasis and East Lansing, MI, USA. copper based enzymatic activity.1 Contact e-mail: [email protected] Mammalian protein possesses two specific binding sites in the unstructured domain: i) octarepeat region2 and ii) neurotoxic 2-oxoglutarate-dependent hydroxylases are mononuclear non-heme peptide fragment.3 In all cases histidine residues play a basic role in Fe(II) enzymes that couple the oxidative decarboxylation of an oxo- the metal protein interactions. Avian proteins contain the acid to the transformation of a primary substrate. The archetype hexapeptide repeats having also one His residue critical for Cu(II) representative of this enzyme family is TauD, an Escherichia coli binding.4 Surprisingly the fish proteins e.g. that of Japanese enzyme that converts taurine (2-aminoethanesulfonate) to sulfite pufferfish may be even more potent Cu(II) binder than those of and aminoacetaldehyde. Recent spectroscopic findings related to mammalians and avian.5 In the latter case the repeat domain is very TauD and its variants will be presented and corresponding insights different than those in human or chicken, but containing multi- into the enzyme mechanism will be described. To illustrate the histidine region is very effective in the interactions with copper. versatility of this group of catalysts, three representative enzymes 1. E. Gaggelli, H. Kozlowski, D. Valensin, and G. Valensin, Chem. from eukaryotic sources will be discussed. Aspergillus nidulans Rev., 106, 1995, 2006. contains XanA which was demonstrated to be a xanthine 2. D. Valensin, M. Luczkowski, et al., Dalton Trans., 1284, 2004. hydroxylase; this enzyme utilizes 2-oxoglutarate-dependent 3. F. Berti, E. Gaggelli, R. Guerrini, A. Janicka, et al., Chem. Eur. J. chemistry rather than the better known molybdopterin system for 13, 1991, 2007. producing uric acid. Trypanosoma brucei, the protozoan responsible 4. P. Stanczak, D. Valensin, et al., Chem. Commun., 3298, 2005. for African sleeping sickness, is known to modify specific thymine 5. P. Stanczak, D. Valensin, et al., Biochemistry, 45, 12227, 2006. bases in its DNA to create the J base; evidence is presented related to the potential use of a 2-oxoglutarate-dependent thymine hydroxylase catalyzing this activity. Finally, humans possess eight homologues to AlkB, an enzyme that repairs alkylation-damaged 123 S54 J Biol Inorg Chem (2007) 12 (Suppl 1):S53–S98 KL12 Living on acetylene: structure and function of acetylene hydratase, a novel bacterial tungsten enzyme Grazyna Seiffert1, Felix TenBrink1, Bernhard Schink1, Albrecht Messerschmidt2, Oliver Einsle3, Peter M. H. Kroneck1, 1Universität Konstanz, Konstanz, Germany; 2MPI Biochemie, Martinsried, Germany; 3Universität Göttingen, Göttingen, Germany. Contact e-mail: [email protected] To date, acetylene is the only hydrocarbon known to be metabolized in the absence and presence of molecular oxygen. The novel W,Fe- S enzyme acetylene hydratase (AH) from the strictly anaerobic bacterium P. acetylenicus stands out from its class in that it catalyzes a non-redox reaction, the addition of water to the C,C triple bond to form acetaldehyde. However, Ti(III)-citrate or dithionite, is required for activity. AH belongs to the dimethylsulfoxide reductase family, and it contains a bis-MGD- ligated W and a [4Fe:4S] cluster, with a redox potential of - 410 ± 20 mV [1]. The 3D structure (1.26 Å) reveals a water molecule at the W site that gets activated by an aspartate to attack acetylene bound in a hydrophobic pocket. A strong shift in pKa of the aspartate residue is required, caused by the [4Fe:4S] cluster. To KL14 access this novel W site, AH evolved a substrate channel distant The molybdenum cofactor: Biosynthesis, function and from where it is found in related Mo and W enzymes [2]. P. deficiency acetylenicus can also insert Mo (but not V) into the bis-MGD Guenter Schwarz, Institute of Biochemistry at the University cofactor of AH, but the specific activity of the Mo isoenzyme was of Cologne, Cologne, Germany. significantly lower. Contact e-mail: [email protected] [1] Boll, M., Schink, B., Messerschmidt, A., Kroneck, P.M.H., Novel bacterial molybdenum and tungsten enzymes: Three- The molybdenum cofactor (Moco) forms the active site of all dimensional structure, spectroscopy, and reaction mechanism, Biol. molybdenum enzymes, except nitrogenase. Molybdenum enzymes Chem., 2005, 386, 999-1006. catalyze important redox reactions in global metabolic cycles. Moco [2] Seiffert, G.B., Ullmann, G.M., Messerschmidt, A., Schink, B., consists of molybdenum covalently bound to one or two dithiolates Kroneck, P.M.H., Einsle, O. Structure of the non-redox-active attached to
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